Efficacy and Safety of Sacubitril/Allisartan for the Treatment of Primary Hypertension

BACKGROUND: The prevalence of hypertension still increases with the very rapidly increasing longevity in some countries, such as China. The control rate remains low. OBJECTIVES: This randomized, double-blind, phase 3 study assessed the efficacy and safety of sacubitril/allisartan, compared with olmesartan in Chinese patients with mild-to-moderate hypertension. METHODS: Eligible patients aged 18 to 75 years (n = 1,197) with mild-to-moderate hypertension were randomized to receive sacubitril/allisartan 240 mg (n = 399), sacubitril/allisartan 480 mg (n = 399), or olmesartan 20 mg (n = 399) once daily for 12 weeks. Patients who completed the 12-week treatment then received another 12-week extended treatment (n = 1,084) and 28-week prolonged treatment (n = 189). The primary end point was a reduction in clinic mean sitting systolic blood pressure (msSBP) from baseline at 12 weeks. RESULTS: Sacubitril/allisartan 240 mg/d provided a greater reduction in msSBP than olmesartan at 12 weeks (between-group difference: -1.9 mm Hg [95% CI: -4.2 to 0.4 mm Hg]; P = 0.0007, for noninferiority). Sacubitril/allisartan 480 mg/d provided a significantly greater reduction in msSBP than olmesartan at 12 weeks (between-treatment difference: -5.0 mm Hg [95% CI: -7.3 to -2.8 mm Hg]; P < 0.001, for superiority). Greater reductions in 24-hour, and daytime and nighttime systolic and diastolic blood pressure were also observed with both doses of sacubitril/allisartan compared with olmesartan (P ≤ 0.001 for 480 mg/d). The blood pressure reductions tended to be dose-dependent for sacubitril/allisartan. Sacubitril/allisartan was well tolerated, and no cases of angioedema or death were reported. CONCLUSIONS: Sacubitril/allisartan is effective for the treatment of hypertension and well tolerated in Chinese patients.